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Decondensing the protamine domain for transcription.

ABSTRACT: Potentiation is the transition from higher-order, transcriptionally silent chromatin to a less condensed state requisite to accommodating the molecular elements required for transcription. To examine the underlying mechanism of potentiation an approximately 13.7-kb mouse protamine domain of increased nuclease sensitivity flanked by 5' and 3' nuclear matrix attachment regions was defined. The potentiated DNase I-sensitive region is formed at the pachytene spermatocyte stage with the recruitment to the nuclear matrix of a large approximately 9.6-kb region just upstream of the domain. Attachment is then specified in the transcribing round spermatid, recapitulating the organization of the human cluster. In comparison to other modifiers that have no effect, i.e., histone methylation, HP1, and SATB1, topoisomerase engages nuclear matrix binding as minor marks of histone acetylation appear. Reorganization is marked by specific sites of topoisomerase II activity that are initially detected in leptotene-zygotene spermatocytes just preceding the formation of the DNase I-sensitive domain. This has provided a likely model of the events initiating potentiation, i.e., the opening of a chromatin domain.

SUBMITTER: Martins RP

PROVIDER: S-EPMC1895951 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Loss of the cleaved-protamine 2 domain leads to incomplete histone-to-protamine exchange and infertility in mice.

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Loss of the cleaved-protamine 2 domain leads to incomplete histone-to-protamine exchange and infertility in mice [cPRM2]

Project description:Protamines are unique sperm-specific proteins that package and protect paternal chromatin until fertilization. A subset of mammalian species expresses two protamines (PRM1 and PRM2), while in others PRM1 is sufficient for sperm chromatin packaging. Alterations of the species-specific ratio between PRM1 and PRM2 are associated with infertility. Unlike PRM1, PRM2 is generated as a precursor protein consisting of a highly conserved N-terminal domain, termed cleaved PRM2 (cP2), which is consecutively trimmed off during chromatin condensation. The carboxyterminal part, called mature PRM2 (mP2), interacts with DNA and together with PRM1, mediates chromatin-hypercondensation. The removal of the cP2 domain is believed to be imperative for proper chromatin condensation, yet, the role of cP2 is not yet understood. We generated mice lacking the cP2 domain while the mP2 is still expressed. We show that the cP2 domain is indispensable for complete sperm chromatin protamination and male mouse fertility. cP2 deficient sperm show incomplete PRM2 incorporation, resulting in a severely altered protamine ratio, retention of transition proteins and aberrant retention of the testis specific histone variant H2A.L.2. During epididymal transit, cP2 deficient sperm seem to undergo ROS mediated degradation leading to complete DNA fragmentation. The cP2 domain therefore seems to be a key aspect in the complex crosstalk between histones, transition proteins and protamines during sperm chromatin condensation. Overall, we present the first step towards understanding the role of the cP2 domain in paternal chromatin packaging and open up avenues for further research.

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